Pulse lineResearch With Heart Logo

Multiple loci influence erythrocyte phenotypes in the CHARGE Consortium.

TitleMultiple loci influence erythrocyte phenotypes in the CHARGE Consortium.
Publication TypeJournal Article
Year of Publication2009
AuthorsGanesh SK, Zakai NA, van Rooij FJA, Soranzo N, Smith AV, Nalls MA, Chen M-H, Köttgen A, Glazer NL, Dehghan A, Kuhnel B, Aspelund T, Yang Q, Tanaka T, Jaffe A, Bis JCM, Verwoert GC, Teumer A, Fox CS, Guralnik JM, Ehret GB, Rice K, Felix JF, Rendon A, Eiriksdottir G, Levy D, Patel KV, Boerwinkle E, Rotter JI, Hofman A, Sambrook JG, Hernandez DG, Zheng G, Bandinelli S, Singleton AB, Coresh J, Lumley T, Uitterlinden AG, Vangils JM, Launer LJ, L Cupples A, Oostra BA, Zwaginga J-J, Ouwehand WH, Thein S-L, Meisinger C, Deloukas P, Nauck M, Spector TD, Gieger C, Gudnason V, van Duijn CM, Psaty BM, Ferrucci L, Chakravarti A, Greinacher A, O'Donnell CJ, Witteman JCM, Furth S, Cushman M, Harris TB, Lin J-P
JournalNat Genet
Volume41
Issue11
Pagination1191-8
Date Published2009 Nov
ISSN1546-1718
KeywordsBlood Pressure, Cell Line, Cohort Studies, Endothelial Cells, Erythrocytes, Gene Expression, Genome, Human, Genome-Wide Association Study, Humans, Hypertension, Phenotype, Polymorphism, Single Nucleotide, Quantitative Trait Loci
Abstract

Measurements of erythrocytes within the blood are important clinical traits and can indicate various hematological disorders. We report here genome-wide association studies (GWAS) for six erythrocyte traits, including hemoglobin concentration (Hb), hematocrit (Hct), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC) and red blood cell count (RBC). We performed an initial GWAS in cohorts of the CHARGE Consortium totaling 24,167 individuals of European ancestry and replication in additional independent cohorts of the HaemGen Consortium totaling 9,456 individuals. We identified 23 loci significantly associated with these traits in a meta-analysis of the discovery and replication cohorts (combined P values ranging from 5 x 10(-8) to 7 x 10(-86)). Our findings include loci previously associated with these traits (HBS1L-MYB, HFE, TMPRSS6, TFR2, SPTA1) as well as new associations (EPO, TFRC, SH2B3 and 15 other loci). This study has identified new determinants of erythrocyte traits, offering insight into common variants underlying variation in erythrocyte measures.

DOI10.1038/ng.466
Alternate JournalNat Genet
PubMed ID19862010
PubMed Central IDPMC2778265
Grant ListP30 DK063491-05 / DK / NIDDK NIH HHS / United States
U01 DK066174 / DK / NIDDK NIH HHS / United States
R01 HL086694 / HL / NHLBI NIH HHS / United States
G0000111 / / Medical Research Council / United Kingdom
R01 HL086694-01A1 / HL / NHLBI NIH HHS / United States
P30 DK063491-039004 / DK / NIDDK NIH HHS / United States
P30 DK063491 / DK / NIDDK NIH HHS / United States
R01 HL086694-02 / HL / NHLBI NIH HHS / United States
R01 HL086694-03 / HL / NHLBI NIH HHS / United States
P30 DK063491-029004 / DK / NIDDK NIH HHS / United States
P30 DK063491-019004 / DK / NIDDK NIH HHS / United States
P30 DK063491-049004 / DK / NIDDK NIH HHS / United States
K24 DK078737 / DK / NIDDK NIH HHS / United States